Riverside Research Institute, the University of Hawaii and Kuakini Medical Center, and the National Center for Scientific Research (Paris, France) propose to continue to investigate, refine, and expand the use of novel quantitative ultrasound methods for discriminating between cancer-containing and cancer-free lymph nodes of cancer patients. Detection of metastatic cancer in lymph nodes is absolutely crucial for accurate staging, prognosis, and treatment planning. Our overall objective is to reduce markedly the unacceptable failure of existing histopathological methods to detect metastases in 25% to 30% of dissected nodes and 50% in nodes with micrometastases. To achieve this objective, we proposed to develop quantitative imaging methods using high-frequency ultrasound in the pathology laboratory to identify regions of dissected nodes that warrant careful histologic examination. We have made exciting progress toward this objective by developing a sensitive and specific ultrasonic method of imaging metastatic disease present in lymph nodes with fine spatial resolution. Our results have shown a remarkable ability to detect cancer in dissected lymph nodes for a broad range of cancer types, and they promise a revolutionary means of guiding pathologists to cancer-containing regions of dissected lymph nodes. The demonstrated ability of our proposed methods to pinpoint metastatic cancer potentially can reduce the occurrence of false-negative determinations drastically when nodes contain micrometastatic disease, which easily can be overlooked using current histopathology methods. Our current results substantially have validated our original hypothesis that the proposed methods can identify cancer- containing regions of dissected nodes with a simultaneous sensitivity and specificity of approximately 90%. These findings provide encouragement that our proposed studies fully achieve our general objective, and they suggest that a simultaneous sensitivity and specificity exceeding 95% in fact may be possible. Therefore, we propose to acquire additional data to expand our existing database and thoroughly validate our findings. We also propose to investigate the feasibility of applying the same techniques at lower frequencies for clinical use in the examination or operating room to identify nodes that warrant biopsy or dissection. In addition, we propose to improve models for ultrasound scattering in lymph nodes using very-high-frequency ultrasonic microscopy and to formulate engineering specifications for a low-cost ultrasound instrument capable of performing node evaluations routinely in the pathology laboratory. In conclusion, this project can benefit lymph-node evaluations for staging, prognosis, and treatment planning of all types of cancers, e.g., breast, colorectal, gastric, pancreatic, lung, thyroid, prostate, etc., as well as sentinel-node dissection procedures, e.g., for breast cancer. The methods we are developing clearly can have a significant beneficial impact on in situ evaluations of lymph nodes examined prior to or during surgery, intra-operative evaluations of regional nodes including sentinel-nodes, and post-operative evaluations of dissected nodes. PUBLIC HEALTH RELEVANCE: Accurate detection of metastases in lymph nodes is essential for cancer staging and treatment planning;however, standard methods of node evaluation may miss small metastases in as many as 50% of nodes that have them. Our proposed ultrasonic methods show promise for reliably detecting all clinically significant node metastases. We will develop and refine these methods for use in office examinations, surgery and pathology.